Feline coronavirus (FCoV) belongs to the Coronaviridae family, a group of enveloped, positive stranded RNA viruses, commonly found in cats. In nature, FCoVexists as two distinct biotypes: feline enteric coronavirus (FECV) and feline infectious peritoneal virus (FIPV), a mutated form of FECV.
FECV infection is widespread in cats, with an estimated 40-80% of cats shedding the virus worldwide. FECV chronically infects the gastrointestinal epithelial cells in cats and is typically transmitted through the fecal-oral route. FECV infection in cats is largely asymptomatic, with some cats experiencing diarrhea, vomiting, loss of appetite, and fever.
The FIPV biotype arises following a single nucleotide polymorphism or deletion that inactivates the viral 3c protease gene in FECV, although mutations within the viral spike protein has also been implicated. Inactivation of the 3c protease alters cell tropism enables the virus to replicate within macrophages, facilitating systemic dissemination of FIPV and the onset of feline infectious peritonitis (FIP).
FIP is a progressive, immune related disease in cats. FIP disease can take the form of “wet” or “dry” FIP. Wet FIP is associated with an inflammation of the visceral serosa and omentum resulting in the exudation of fluids into the abdomen and/or chest cavities. Dry FIP is characterized by granulomatous involvement of paracnchymatous organs such as the liver, central nervous system or eyes. The development of either the wet or dry form of FIP is invariably fatal.
FIP is a major problem in environments with large cat densities such as, multi-cat households, catteries, shelters, and cat rescue facilities. The disease is most prevalent in younger cats (<3 years old), and particularly kittens, due to the higher levels of replicating FECV, which increases the likelihood of mutation to the FIPV biotype, as well as reduced resistance to viruses harboring those mutations. FIP is a leading cause of death in cats under 2 years of age and is estimated to kill between 0.3 and 1% of cats worldwide.
Currently, there are no approved vaccines or effective antiviral therapies for the treatment of FIP. Therefore there is a significant need for the development of compounds to treat FIP in cats. Without being bound, it is hypothesized that treating FCoV or FIPV would prevent or treat FIP.